探討芝麻素抑制人類膀胱腫瘤的惡性進展

何肇晏¹、黃一勝^1,3,4、仇光宇¹、蔡德甫¹、張安辰²

¹新光醫院 泌尿科，²轉譯醫學中心；³台北醫學大學 醫學院；⁴輔仁大學 醫學院

Study on sesamin inhibiting malignant progression of human bladder tumor

Chao-Yen Ho¹, Thomas I-Sheng Hwang^1,3,4, Kuang-Yu Chou¹, Te-Fu Tsai¹, and An-Chen Chang²

Department of Urology¹ and Translational Medicine Center², Shin Kong Wu Ho-Su Memorial Hospital; Department of Urology, Taipei Medical University³; Division of Urology, School of Medicine, Fu-Jen Catholic University⁴, Taipei, Taiwan.

Purpose:

Bladder cancer (BC), one of the most common urological neoplastic disorders in men, has a low survival rate because of its tendency to metastasize. Sesamin, a major bioactive compound in sesame seeds, has been reported to have anti-proliferative, pro-apoptotic and anti-metastatic activities in cancers. Matrix metalloproteinases (MMPs) involved in tumor progression have been discussed; however, sesamin inhibited BC cells invasiveness and tumor growth via MMPs suppression has not been discussed.

Materials and Methods:

Human BC cell lines UMUC3, 5637 and T24 were obtained from the Bioresource Collection and Research Center (BCRC; Hsinchu, Taiwan). Resazurin-based cell viability assay was performed to measure cell survival rate. Western blot was used to measure the levels of indicated protein expression. Cell migrative and invasive ability was performed by Wound healing and Transwell migration/invasion assay, respectively. Animal model was used to analyze bladder tumor growth after sesamin treatment.

Results:

The study showed that sesamin, when administered for a prolonged period, reduced the survival rate of BC cells, as indicated by the results of the colony formation assay. Furthermore, sesamin inhibited the migration and invasion of BC cells by down-regulating MMP2 expression, but it did not affect the expression of other metastasis-related genes such as MMP9, MMP11, N-cadherin, and VEGF-C. The mechanism of action for sesamin was discovered to be the inhibition of MMP2 protein expression through the STAT3 signaling pathway. Pretreatment of BC cells with a STAT3 activator (Colivelin) counteracted the inhibitory effect of sesamin on MMP2 expression, migration, and invasion. Finally, in vivo experiments showed that sesamin reduced the growth of bladder cancer tumors.

Conclusions: 

This study demonstrated the anti-tumor effect of sesamin by showing that sesamin inhibits BC cell invasiveness in vitro and tumor growth in vivo. Sesamin has the potential to be applied to the clinical treatment of BC.